As immunocompetent cells of the brain, microglia are able to counteract the damaging effects of amyloid-beta in Alzheimer's disease by phagocytosis-mediated clearance of protein aggregates. The survival and health of microglia are therefore crit. for attenuating and preventing neurodegenerative diseases. In a microglial cell line pretreated with St. John's wort (Hypericum perforatum L.) ext. (HPE), the cell death evoked by treatment with amyloid-beta (25-35) and (1-40) was attenuated significantly in a dose-dependent manner. Investigation of the single compds. in the ext. revealed that the flavanols (+)-catechin and (-)-epicatechin increase cell viability slightly, whereas the flavonol quercetin and its glycosides rutin, hyperosid and quercitrin showed no effect on cell viability. In contrast, at the same concn., the flavonoids reduced the formation of amyloid-induced reactive oxygen species in microglia, indicating that improvement of cell viability by the catechins is not correlated to the antioxidant activity. No influence of HPE on the capacity of microglia to phagocytose sub-toxic concns. of fibrillar amyloid-beta (1-40) was obsd. Other expts. showed that HPE, (+)-catechin and (-)-epicatechin can alter cellular membrane fluidity and thereby may have a beneficial effect on cell health. Our findings provide in vitro evidence that treatment esp. with the complex plant ext. HPE may restore or improve microglial viability and thereby attenuate amyloid-beta mediated toxicity in Alzheimer's disease
